Papovaviruses are virtually universal, usually benign agents in human populations. In immunologically impaired patients, however, this group of viruses is capable of causing a rare, fatal, central nervous system infection, progressive multifocal leukoencephalopathy (PML) and has been associated by some investigators with neoplastic disease. Little is known, however, about the pathogenesis of pathogenesis of papovavirus infection in man or about the conditions under which members of this usually benign group of viruses may cause clinical significant human disease. The present research project involves investigation of an analogous papovavirus, K virus of mice, in its natural host as a possible model for human infection. Studies to date have resulted in the development of an in vitro assay for K virus infectivity using primary cultures of mouse embryo cells and have characterized the fatal infection which K virus causes in newborn animals, demonstrating a systemic infection with involvement of multiple organs including brain. Work currently in progress suggests that a similar, less severe infection occurs in older animals in whom the virus does not produce clinically significant diseases and that, in older suckling animals, virus persists in intestine, kidney, brain and lung for at least 76 days after inoculation. During the second year of the award, we plan to complete the studies of K virus infection in older animals and begin experiments to determine the effect of immuno-suppression on K virus infection, to ascertain whether or not the virus is capable of producing transplacental infection, and to evaluate the ability of the virus to produce cell transformation in experimental animals and in tissue culture. The experiments planned will be carried out using histologic and ultrastructural techniques, fluorescent antibody studies of infected tissues, and the in vitro assay system described above.